Patients who have had generalized systemic reactions due to insect stings often have negative skin tests with available whole-body insect extracts. An IgE pathogenesis of these reactions might be clarified with the use of a more appropriate testing antigen, i.e., pure venom or fractions of venom. Alternatively these reactions may have other immunologic or non-immunologic mediators. Venom and its fractions will be used for diagnostic testing both by in vitro and in vivo methods. Similar methods will be utilized to assay the results of specific immunotherapy by analyzing pre and post treatment blood samples to measure humoral and cellular responses. Studies of beekeepers may further elucidate the immune mechanism. Cellular mechanisms and non IgE humoral mehcanisms will also be investigated as immunological mediators. Non-immunologic reactions (if such exist) may be due to deficiencies of inhibitors which normally destroy the pharmacologically active substances in the venom. Assay of these inhibitors in the sera and/or white cells will be studied. We hope to (1) identify the specific allergic component; (2) elucidate the pathogenesis of these reactions; (3) establish guidelines for definitive therapy; and (4) establish methodology for standardization of insect allergen extracts.